Diabetes Forecast

The Future Is (Almost) Now

What's coming next for managing your diabetes

By Erika Gebel, PhD ,

(Tomorrow's) Medicine Cabinets

Discovered in 1921, insulin continues to be the most potent medicine for people with diabetes. But there is still only one way to get it into the human body, and that means needles. Those needles have already been engineered to be smaller and less painful than ever before, but scientists continue to work on needle-free delivery systems that would be easier to use and eliminate the need for injections.

One such product, the inhalable insulin Exubera, was launched in 2006 but taken off the market after it failed to catch on. Though some users embraced this technology, it's thought that the delivery tube system was a turnoff to others. And some doctors worried that with long-term use Exubera might damage the lungs. Still, scientists haven't given up on inhalables. At least one other version is currently in development.

Insulin throat spray is another product working its way through laboratories and clinical trials. Since it's not inhaled, it doesn't pose a threat to the lungs, and in studies it has demonstrated effectiveness on par with inhaled insulin. One spray, called Oral-lyn, from Generex, is already available in some countries but not yet in the United States.

A third insulin delivery method being tested involves skin, but minus the needles. The idea is something like a nicotine patch for insulin. The challenge: how to get past the skin's very efficient barrier system, since insulin molecules are much bigger than nicotine. Scientists are trying to chauffeur insulin through skin using chemicals, electricity, and ultrasound.

Of course, the holy grail would be an insulin pill. Unfortunately, the digestive tract attacks insulin—a protein—as it would a piece of steak. Researchers are attempting to trick the digestive system by disguising insulin in a protective "cloak." They are also attempting to change insulin's structure ever so slightly so that it will pass unnoticed through the digestive gauntlet.

Other (Pharmaceuticals)

Currently, there are six types of pills that can help people manage type 2 diabetes: sulfonylureas, meglitinides, metformin, thiazolidinediones, alpha-glucosidase inhibitors, and DPP-4 inhibitors. There are also two injected medications for people with diabetes: pramlintide and exenatide.

What might you see next at the pharmacy? At this year's American Diabetes Association Scientific Sessions, researchers talked about four pharmaceutical classes on the horizon for treating high blood glucose: sodium-glucose cotransporter inhibitors, glucokinase activators, glucagon receptor antagonists, and sirtuins. Here's how they would work:

Sodium-glucose cotransporter inhibitors would compromise the ability of the kidneys to reabsorb glucose, allowing excess glucose to pass directly into the urine.

Glucokinase activators would trigger an increase in insulin production by the pancreas and would also lower blood glucose by increasing glucose uptake by the liver.

Glucagon receptor antagonists would lower blood glucose by blocking the work of glucagon, a hormone that increases blood glucose.

Sirtuins are proteins that play many roles and that are believed to have an antiaging effect. Resveratrol, a chemical found in red wine, is a sirtuin activator. Some preliminary studies have shown that sirtuin activators may help lower blood glucose in people with type 2 diabetes.

The (iPod-ization) of Diabetes

As information technology rapidly improves, diabetes gadgetry is riding its wake. Take the new OneTouch Ping, a blood glucose management system with a meter that wirelessly transmits data to an integrated insulin pump. Or the Glucophone, a cell phone with built-in blood glucose meter that allows users to send results to a health care provider, family member, or anyone else they designate. Similarly, the InterMed Patient Data Handler wirelessly receives blood glucose readings from a meter and then automatically transmits them to a central server each night. InterMed's software then analyzes the data and e-mails a report to both patient and provider.

These innovations reflect the high-tech future of diabetes care, says Adam Greene, developer of a new Web site—SweetSpot.dm—that deals in data management and social networking for people with diabetes. As people integrate other parts of their life with the Internet, managing diabetes is sure to follow. For example, right now, says Greene, "people are not used to managing health online at all. But that's starting to change."

Greene's site is a case in point. For about $10 a month, SweetSpot allows you to upload health information manually or directly from compatible blood glucose meters. It will plot the data in a number of different ways, so you can watch for patterns. Perhaps more groundbreaking, however, is the social networking aspect: The site also acts like a kind of Facebook for people with diabetes, providing a way to interact and share information. Greene plans to bring health care providers into the equation through partnerships with hospitals and online health databases such as Google Health. He's betting that online health tracking will soon be as common as online banking.

Some of the technological innovations coming down the road sound a bit more, well, futuristic: At this year's ADA Scientific Sessions, Medtronic unveiled a prototype for a glucose-sensing car that sounds an alarm if the driver's blood glucose starts to dip. A continuous glucose monitor chip worn under the skin wirelessly transmits readings to a microchip in the dashboard.

An (i-Pancreas?)

Despite all the technological advances in the field of diabetes care, no one has figured out how to fully automate blood glucose control. Sure, there are insulin pumps and continuous blood glucose monitors, which take measurements every few minutes around the clock. But the person with diabetes still has to decide when to administer insulin and how much to take. And even under the best of circumstances, people can make mistakes.

"What we need is to make today's devices much smarter," says Aaron Kowalski, PhD, research director with the Juvenile Diabetes Research Foundation Artificial Pancreas Project. Kowalski envisions a future that includes an "i-Pancreas," an artificial pancreas as chic and functional as an iPod. One sticking point thus far has been coming up with software smart enough to integrate the glucose monitor with a pump. But even now, says Kowalski, the algorithms researchers have developed are better at controlling blood glucose than most humans are.

Kowalski imagines that the first artificial pancreas will be semiautomatic, able to detect hypoglycemia and cut off the flow of insulin if blood glucose is going low. Another more sophisticated system could follow, but a fully automated pancreas would need faster-acting insulin to be really effective, Kowalski says. That's because in people without diabetes, the mere sight of food primes the digestive system and starts the insulin flowing. The other obstacle is getting the insulin into the system as quickly as the pancreas would normally do it. Current pumps can't deliver insulin nearly fast enough. Scientists are working to solve this problem, and some are even trying to develop implantable monitors and pumps, he says.

Beyond (Band-Aids)

No matter how cutting-edge, all of these innovations amount to sophisticated Band-Aids. The ultimate goal is to cure diabetes.

Scientists already know that type 2 diabetes can be prevented and even thrust into remission through changes in lifestyle. Obesity is one trigger, and studies have shown that weight loss through diet, exercise, medications, and in some cases surgery can be an effective tool for treating type 2 diabetes.

However, not every overweight person develops diabetes, and lean people are not immune; there is a strong genetic component. Scientists have uncovered several type 2 diabetes genes, and more discoveries are likely to follow. An understanding of the biochemical and genetic underpinnings of the disease may offer new ways to prevent and cure type 2 diabetes. But while some scientists say that the future of medicine may include individualized care based on a person's genetic makeup, for people with diabetes, this kind of personalized treatment will be particularly difficult to achieve due to the complexity of diabetes genetics.

One potential therapy that may work regardless of genetic makeup would involve replacing lost insulin-producing cells through transplantation. This could be effective because people with type 1 diabetes are victims of aberrant behavior by their own immune systems. Specifically, autoimmune diabetes occurs when the immune system attacks the insulin-producing beta cells of the pancreas and destroys them. No one knows exactly why this happens, but both genetics and environment likely play a role.

Scientists already have met with some success in the transplantation of either whole pancreases or islet cells; however, donors are in short supply and the benefits so far have been fleeting. Pig pancreases and stem cells are two possible sources of insulin-producing cells. For transplantation to be successful, researchers must devise methods to protect the newly transplanted cells from the immune system.

Another way to thwart diabetes may be to shut down the anti-beta cell autoimmune process itself, before irrevocable damage is done, but without knocking out the precious immune system altogether. To this end, the notion of a "diabetes vaccine" is gaining popularity, although the word "vaccine" is a bit of a misnomer. Typically, vaccines are pieces of viruses that trigger an immune response, thereby providing subsequent immunity against future viral intrusion. A diabetes vaccine follows a rather different approach.

There are several types of vaccines in various phases of development, and most use a similar strategy: shut down the T cells (the immune system's key attack cells) that destroy the insulin-producing cells in the pancreas. Massimo Trucco, MD, professor of pediatrics at the University of Pittsburgh, has recruited the immune system's dendritic cells in his experimental diabetes vaccine. In the early stages of type 1 diabetes, dendritic cells bring pieces of beta cells to the T cells and activate their killer instinct.

Trucco hopes to block this destructive interaction. "We grow dendritic cells, but we block them from communicating with the T cells," says Trucco. "Then the T cells get confused and paralyzed. They cannot move." Trucco is trying to get his study included under the umbrella of TrialNet, an international multicenter project that has the end goal of curing type 1 diabetes.

"I think we'll learn in the next 5 to 10 years how we can prevent quite a number of cases of type 1 diabetes," says Richard Kahn, PhD, chief scientific and medical officer at the ADA. "I'm optimistic because a number of prevention trials are underway and sooner or later something is going to hit."

Type 2 diabetes will be harder to tackle, Kahn says, although curbing the obesity epidemic will help. Drugs that prevent weight gain should be available within the next decade, he predicts. At the same time, lifestyle changes have been proven to prevent type 2 diabetes. "A revolution to follow will be changing the health care system to be able to identify individuals at risk and target them for lifestyle interventions," says Paris Roach, MD, associate professor of clinical medicine in the Division of Endocrinology and Metabolism at the Indiana University School of Medicine in Indianapolis.

Indeed, while individualized genetic medicine and diabetes vaccines may be years away, many of science's most exciting diabetes innovations are just around the corner. An artificial pancreas, sophisticated online health management tools, and drugs that work in new and interesting ways to improve blood glucose control are among the products that researchers say are coming soon.

That means one thing is crystal-ball clear: The future is bright for people managing diabetes.



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